Pioneer in Synthetic Biology discusses how to be a successful innovator

George Church helped revolutionized the study of DNA by exponentially reducing the cost of sequencing it. George Church came up with an idea he called “multiplexing” to sequence dozens to millions of pieces of DNA simultaneously—processing them all in the same tube—rather than one at a time, which had been the accepted method.

George McDonald Church is an American geneticist, molecular engineer, and chemist. He is Professor of Genetics at Harvard Medical School, Professor of Health Sciences and Technology at Harvard and MIT, and founding core member of the Wyss Institute for Biologically Inspired Engineering at Harvard University. He is widely regarded as a pioneer in personal genomics and synthetic biology. Church has co-authored more than 290 publications and 50 patents. Church is or has been involved in founding many very successful (13 biotech) startups.

Over many decades George Church has shown a pattern of inspiration and persistence that became a creative habit.

“I’ll drop something for a while, a year or maybe several years, and then pick it up again,” he says. “I think that’s the way successful innovators work. They keep juggling ideas, keeping them in the air, in the back of their mind, to inspire them or enable new recombinations.”

He devotes most of his energy to encouraging his team to innovate.

“A lot of people can’t be bothered with innovation,” he says. “It’s a nuisance, in certain ways. It usually brings a lot of anxiety and other problems—the kinds of things that prevent the average person from setting aside the time and taking the risks.” But for Church’s lab, there’s no alternative, he says. It’s the only way forward.

In April, the Broad Institute, where Church holds a faculty appointment, was awarded a patent for a new method of genome editing called CRISPR (clustered regularly interspersed short palindromic repeats), which Church says is one of the most effective tools ever developed for synthetic biology. By studying the way that certain bacteria defend themselves against viruses, researchers figured out how to precisely cut DNA at any location on the genome and insert new material there to alter its function. Last month, researchers at MIT announced they had used CRISPR to cure mice of a rare liver disease that also afflicts humans. At the same time, researchers at Virginia Tech said they were experimenting on plants with CRISPR to control salt tolerance, improve crop yield, and create resistance to pathogens.

The possibilities for CRISPR technology seem almost limitless, Church says. If researchers have stored a genetic sequence in a computer, they can order a robot to produce a piece of DNA from the data. That piece can then be put into a cell to change the genome. “You don’t even have to take the genome out of the organism,” Church says. “You can change it essentially with the motor running. It’s like you throw a piston into a car and it finds its way to the right place and swaps out with one of the pistons while the motor’s running.”

Church believes that CRISPR is so promising that last year he co-founded a genome-editing company, Editas, to develop drugs for currently incurable diseases. It was the latest of 13 biotech firms that he’s helped found since 2005.

How to bring back the Wooly Mammoth and Neanderthals

Thanks to another groundbreaking technology developed in Church’s lab, the notion of resurrecting extinct animals such as the woolly mammoth could also soon become a reality. Mammoths disappeared only about 3,400 years ago, and their remains—including bones, teeth, hair, skin, and fat—have been found across Siberia and Alaska. Using DNA from these remains, scientists have reconstructed a significant portion of the mammoth’s genome, which they’ve discovered is closely related to that of the Asian elephant.

The easiest way to create a mammoth, Church argues, would be to start with an elephant’s genome and gradually transform it into a mammoth’s. Using the same cut-and-paste methods as those proposed for gene therapy, researchers would selectively replace elephant genes with key mammoth genes, such as those for woolly hair rather than stubby elephant bristles. A small team in Church’s lab is already focusing on transferring three mammoth genes—for subcutaneous fat, cold-adapted hemoglobin, and long hair—to a living elephant cell line. This process may be accelerated by what Church calls MAGE technology (multiplex automated genomic engineering), which some have nicknamed the “evolution machine.” Rather than carrying out substitutions one at a time, MAGE allows researchers to simultaneously introduce new genetic material on a wholesale basis. The practical result, Church told a group at National Geographic last year, could soon be “a hybrid elephant that has the best features of modern elephants and the best features of mammoths.”

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